1) Innate Immunity Flashcards
True or False. Innate immunity is specific.
FALSE. innate immunity is non-specific, meaning everyone’s response is nearly the same
What is the response time to innate immunity?
immediate
What are the cells involved with innate immunity?
1) phagocytes (macrophages)
2) neutrophils
3) natural killer cells
Is innate immunity preformed or takes time to develop?
preformed so it’s ready to go immediately
How does innate immunity get amplified? How is this different than adaptive immunity?
the cells are recruited to the site of injury in innate immunity. amplification in adaptive immunity is done by clonal expansion
What is known as the initial response to microbes that prevents, controls or eliminates infection of the host by many pathogens
innate immunity
Molecular structures that are produced by microbial pathogens that are recognized by innate immunity
PAMPs (pattern-associated molecular patterns)
What PAMP is expressed by gram negative bacteria?
LPS (lipopolysaccharide)
Endogenous molecules that are produced by or released from damaged and dying cells
damage-associated molecular patterns (DAMPs)
What recognizes PAMPs?
pattern recognition receptors on host cells
What pattern recognition receptor binds to LPS?
TL4 (toll-like receptor)
TL4 is found on the surface of which cells?
macrophages
What are some locations where toll-like receptors (TLR) are found?
1) cell membrane
2) inside endosomes
3) cytosol
4) all throughout the cell
Toll-like receptors are a subset of what?
pattern recognition receptors
The binding of PAMP to TLR leads to what?
signal transduction cascade that results in the activation of transcription factors NFkB and IRFs (interferon response factors)
What does the activation of NFkB lead to?
activates cell to produce pro-inflammatory cytokines
What does the activation of IRF lead to?
production of Type I IFN (interferons), which are cytokines that have antiviral properties
What is an inflammasome?
It’s an intracellular pattern recognition receptor complex that leads to the formation of IL-1, which is an important cytokine that leads to inflammation
Autoinflammatory syndromes are due to dysregulated activation what?
inflammasome gets a gain-of-function mutation that leads to excessive expression of IL-1, causing recurrent attacks of fever and localized inflammation
What is the treatment for autoinflammtory syndromes?
IL-1 antagonists
What are the different types of physical barriers (3)?
1) mechanical
2) chemical
3) microbiological
What areas of the body is considered epithelial barriers?
skin, gut, lungs, eyes and nose
What type of cellular junctions do epithelial cells have?
tight junctions that prevent microbes from passing through
How does ciliary action work as a mechanical barrier to infection?
the respiratory tract is lined with cilia that are constantly pushing mucous up and out, thus preventing pathogens from attachment and invasion
What mechanical barrier do skin and gut have along with epithelial cells?
longitudinal flow of air or fluid
What do epithelial cells produce that can impede entry of microbes?
anti-microbial chemicals
What are defensins and cathelicidins, what functions do they have?
anti-microbial peptides produced by epithelial cells; these are toxic to microbes and can activate leukocytes to promote inflammation
What do lysozymes do?
they break down peptidoglycans (found in bacterial cell walls)
What is microbiome?
includes all of the commensal bacteria that normally reside in/on epithelial barriers, can also include viruses, fungi and protozoa
What are the three professional phagocytes?
1) neutrophils (polymorphonuclear leukocytes, PMN)
2) monocyte/macrophage (mononuclear phagocyte)
3) dendritic cells
Which phagocytes are the first to respond to pathogens?
PMN (neutrophils)
What is the life expectancy of neutrophils?
short-lived (24-48 hours)
What are monocytes derived from and where?
hematopoietic stem cells in bone marrow
What is the life expectancy of macrophages?
long-lived (months)
Where are macrophages found?
in all tissues
What are dendritic cells?
they are antigen presenting cells. they phagocytose pathogens or antigens and migrate to lymph nodes to present antigens to lymphocytes
What is the first step in generation of an immune response?
phagocytosis
True or false. macrophages phagocytize dead neutrophils
True. they phagocytize them to prevent them from releasing toxic chemicals
What leukocyte makes up the most of circulating leukocytes?
PMN, about 59%
What are the steps to phagocytosis?
1) target recognition
2) binding and signaling
3) actin rearrangement
4) engulfing leading to zippering or sinking of the particle into the phagocyte
5) destroy particle by breaking it down
What are opsonins?
soluble proteins that recognize phagocytic targets and coats them
How do opsonins mediate phagocytosis?
they have specific receptors that are recognized by phagocytes. once they coat a target particle, phagocytes bind to them. opsonized targets are engulfed much more efficiently than non-opsonized targets
What are the major opsonins in blood?
complement component C3b and antibody IgG
What are the anti-microbial functions of phagocytic cells (4)?
1) acidification
2) toxic oxygen-derived products
3) toxic nitrogen oxides
4) lysozymes
Describe the events after engulfment of target particle by a phagocyte
once engulfment of particle occurs, it is called a phagosome, which fuses with a lysosome to form a phagolysosome
What is the pH of a phagolysosome and what is its significance?
3.5-4.0
bacteriostatic or bactericidal
What is the function of NADPH oxidase?
they generate ROS that are toxic to microbes
Hypohalite OCl- is a type of …
toxic oxygen-derived products
What happens when someone has deficiency in expression or function of NADPH oxidase?
chronic granulomatous disease (CGD). inability to generate ROS which means defect in killing of intracellular bacteria, leading to increased susceptibility to bacterial infection
When is toxic nitrogen oxides produced?
nitric oxide is produced from activated macrophages leading to release of proinflamatory cytokines such as TNF
What is the most important activator for macrophages?
IFN- gamma
What are some characteristics of natural killer cells?
1) large, granular lymphocytes
2) non-specific
3) kill virus-infected cells and certain tumor cells
When do NK cells know when a cell has been infected?
cell is lacking Class I MHC
What receptor activates NK cells to kill?
CD16 (Fc-gamma RIII)
CD16 is expressed by which cell type and what does it bind? What is this process called?
CD16 is expressed by NK cells and it binds to IgG, which binds to antigens expressed on an infected cell. This process is antibody-dependent cell-mediated cytotoxicity (ADCC)
Which cytokine is released by macrophages that activates NK cells?
IL-12
IL-12 stimulates NK cells to produce and release what cytokine?
IFN -gamma, which in turn stimulates macrophages
Innate lymphoid cells are located …
at barriers and they make cytokines
Majority of our bodies’ innate lymphoid cells are alpha-beta, the others are…
1) gamma-delta T cells - these cells are monospecific located in skin and mucosa (epithelial barriers)
2) NK T cells have characteristics of both NK cells and T cells, produces cytokines, and some recognize lipid antigens
What are the three functions of complement?
1) pores in the cell surface –> death by osmotic lysis
2) opsonization
3) stimulate inflammatory reactions
Which complement molecules recruit and activate leukocytes?
C3a and C5a
Which complement molecule is involved with opsonization?
C3b
What are the three pathways of complement?
1) alternative (spontaneous)
2) classical (antibody)
3) lectin (sugars on pathogens)
Which two antibodies can activate the classical complement pathway?
IgG and IgM
Can stand-alone antibodies activated complement?
NO, antibodies must be bound to surface of pathogens in order to activate complement
Which antibody is more efficient, IgG or IgM?
IgM (only 1 IgM is needed while 2 IgGs are needed)
What is the recognition component of classical pathway?
C1q
Which complement component is spontaneously cleaved in alternative pathway?
C3 –> C3a (anaphylatoxin) + C3b (moves on to next step)
True or False. All 3 complement pathways lead to the same effector functions.
TRUE
What causes paroxysmal nocturnal hemoglobinuria?
uncontrolled activation of complement system (lack DAF and CD59)
All 3 complement pathways converge to which complement molecule?
C3 –> cleaved by C3 convertase
Deficiency in classical pathway (C1, C2, C3) will lead to…
immuno-complex disease such as lupus
Deficiency in mannose-binding lectin pathway will lead to…
susceptibility to bacterial infections in childhood
Deficiency in alternative pathway (factor D and factor P) will lead to…
susceptibility to bacterial infections with Nisseria and pyogenic (pus-forming) bacteria, but no immuno-complex disease
Deficiency in C3 will lead to …
similar to deficiency with alternative pathway, but sometimes with immuno-complex disease
Deficiency in MAC (membrane-attack components, C5-C9) will lead to …
susceptibility to Nisseria bacteria only (N. meningitis and N. gonorrhoeae)
What are cytokines?
proteins made by cells that affect the behavior of other cells, mode of communication for immune system
TNF, IL-1, and IL-6 are all what kind of cytokines?
pro-inflammatory
IFN-alpha and IFN-beta are both which kind of cytokines?
Type I. Anti-viral
What biological actions do type 1 IFNs have?
1) inhibit viral replication via a paracrine action
2) enhance cytolytic capability of NK cells
3) increase cellular expression of class I MHC molecules
